Inducing drug-free remission in patients with peripheral spondyloarthritis

SPondyloArthritis: Inducing Drug-free Remission by Early TNF-Alpha BloCkade Under Guidance of Single Cell RNA Sequencing and Epigenetic Profiling. "The SPARTACUS Trial"

This study is testing whether starting treatment with a new type of medication right away can help people with peripheral spondyloarthritis go into remission without needing to rely on drugs.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 112 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University Hospital, Ghent (Academic / other)
• Drugs / interventions: golimumab, methotrexate, adalimumab
• Locations: 6 sites (Aalst and 5 other locations)
• Trial ID: NCT04435288 on ClinicalTrials.gov

What this trial studies

The SPARTACUS study aims to evaluate the effectiveness of two treatment strategies for patients with peripheral spondyloarthritis (pSpA). It will compare a conventional step-up approach using synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) with an early treatment strategy that introduces biological DMARDs (bDMARDs) right away. The study will be conducted over 48 weeks and will involve a randomized, double-blind, active-comparator design to assess the superiority of early treatment with TNF inhibitors like golimumab. The goal is to identify the optimal timing for initiating bDMARDs to achieve drug-free remission.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 diagnosed with peripheral spondyloarthritis who meet specific ASAS classification criteria.

Not a fit: Patients with conditions that do not meet the ASAS criteria for peripheral spondyloarthritis or those outside the age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment paradigm that allows patients to achieve remission without the need for long-term medication.

How similar studies have performed: Previous studies have shown promising results with early treatment strategies in similar patient populations, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

SPARTACUS Phase A: "Remission-Induction Phase"

A subject will be eligible for study participation if all of the following criteria are met:

* Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
* Subjects must be between 18 and 65 years of age.
* Subjects must have been diagnosed with peripheral spondyloarthritis by the treating rheumatologist.
* Subjects must meet the ASAS classification criteria for peripheral spondyloarthritis: subjects must have current arthritis (asymmetric or predominantly in the lower limbs) or current enthesitis (except for enthesitis only along the spine, sacroiliac joints and/or chest wall) or current dactylitis plus at least 1 of the following SpA features:

  * Anterior uveitis confirmed by an ophthalmologist (past or present)
  * Crohn's disease or ulcerative colitis diagnosed by a gastroenterologist (past or present).
  * Evidence of preceding infection (acute diarrhea or non-gonococcal urethritis or cervicitis 1 month before arthritis).
  * Psoriasis diagnosed by a dermatologist (past or present).
  * HLA B27 positivity
  * Sacroiliitis by imaging defined as bilateral grade 2-4 or unilateral grade 3-4 sacroiliitis on plain radiographs, according to the modified New York criteria or active sacroiliitis on MRI according to the ASAS consensus definition (ref of addendum).
* Subjects must have had onset of peripheral SpA symptoms ≤12 months prior to the screening visit.
* Subjects must have active disease at screening defined by Patient Global Assessment of Disease Activity Numerical Rating Scale (NRS) ≥ 4 and Patient Global Assessment of Pain NRS ≥ 4. At the baseline visit patients will be clinically evaluated to exclude spontaneous clinical remission.
* In subjects with concurrent axial SpA symptoms, the peripheral SpA symptoms must be the predominant symptoms at study entry based on the Investigator's clinical judgment.
* Subjects must have a negative PPD test (or equivalent) and chest radiography (anteroposterior and lateral view) at screening. If the subject has a positive PPD test (or equivalent), has had a past ulcerative reaction following PPD placement and/or a chest radiography consistent with prior TB exposure, the subject must initiate, or have documented completion of a course of anti-TB therapy.
* Women of childbearing potential or men capable of fathering children must be using adequate birth control measures during the study and for 3 months after receiving the last administration of study agent.
* Subject is judged to be in good health as determined by the principal investigator based upon the results of medical history, physical examination, laboratory profile, and chest x-ray (CXR) performed during screening.
* Subjects must be able and willing to self-administer SC injections or have a qualified person available to administer SC injections.

SPARTACUS Phase B: "Drug-Free Remission Phase"

A subject will be eligible for phase B of the study if all of the following criteria are met:

* Subjects must have participated in SPARTACUS Phase A.
* Subjects must have reached a status of sustained clinical remission (defined as absence of clinical arthritis, enthesitis and dactylitis at 2 consecutive 'major' visits with an interval of 12 weeks).

Exclusion Criteria:

* Medical history of inflammatory arthritis of a different etiology than peripheral spondyloarthritis (e.g. rheumatoid arthritis, systemic lupus erythematosus, gout, ...).
* Prior adequate treatment with methotrexate and/or sulphasalazine.
* Prior exposure to any biologic therapy with a potential therapeutic impact on SpA.
* Treatment with any investigational drug of chemical or biological nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to the Baseline Visit.
* Subject is taking or has taken prohibited medications as outlined in Table 1 without meeting the mandatory washout period(s) relative to the baseline visit.
* Infection(s) requiring treatment with intravenous (iv) anti-infective agents within 30 days prior to the Baseline visit or oral anti-infectives within 14 days prior to the baseline Visit.
* Have a known hypersensitivity to human immunoglobulin proteins or other components of golimumab.
* History of central nervous system (CNS) demyelinating disease or neurologic symptoms suggestive of CNS demyelinating disease.
* History of listeriosis, histoplasmosis, chronic or active Hepatitis B infection, Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active TB.
* (History of) chronic heart failure, including medically controlled, asymptomatic CHF.
* History of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
* Have received any live virus or bacterial vaccination within 3 months prior to the first administration of study agent; patients who are expected to receive such vaccinations during the trial, or within 3 months after the last administration of study agent.
* Positive serum pregnancy test at screening.
* Female subjects who are breast-feeding.
* Clinically significant abnormal screening laboratory results as evaluated by the Investigator.
* Positive anti-cyclic citrullinated peptide (anti-CCP) antibody at screening if the titers are crossing 3 times the upper limit of normal.
* Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
* Subject with current symptoms of fibromyalgia that would confound evaluation of the patient.

Where this trial is running

Aalst and 5 other locations

• ASZ Aalst — Aalst, Belgium (Not_yet_recruiting)
• AZ Sint-Jan — Brugge, Belgium (Not_yet_recruiting)
• AZ Maria Middelares — Gent, Belgium (Not_yet_recruiting)
• UZ Ghent — Gent, Belgium (Recruiting)
• UZ Leuven Gasthuisberg — Leuven, Belgium (Recruiting)
• ZNA Jan Palfijn — Merksem, Belgium (Not_yet_recruiting)

Study contacts

• Principal investigator: Dirk Elewaut, Prof. dr — UZ Ghent
• Study coordinator: Kristel De Boeck

Conditions Peripheral Spondyloarthritis